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PMID: 9858521 Published · ppublish English Journal Article

Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth.

The Journal of experimental medicine ·Vol. 188 ·No. 12 ·1998-12-21 ·Pages 2349-56

Pike SE, Yao L, Jones KD, Cherney B, Appella E, Sakaguchi K, Nakhasi H, Teruya-Feldstein J, Wirth P, Gupta G, Tosato G

Abstract

An endothelial cell inhibitor was purified from supernatant of an Epstein-Barr virus-immortalized cell line and identified as fragments of calreticulin. The purified recombinant NH2-terminal domain of calreticulin (amino acids 1-180) inhibited the proliferation of endothelial cells, but not cells of other lineages, and suppressed angiogenesis in vivo. We have named this NH2-terminal domain of calreticulin vasostatin. When inoculated into athymic mice, vasostatin significantly reduced growth of human Burkitt lymphoma and human colon carcinoma. Compared with other inhibitors of angiogenesis, vasostatin is a small, soluble, and stable molecule that is easy to produce and deliver. As an angiogenesis inhibitor that specifically targets proliferating endothelial cells, vasostatin has a unique potential for cancer treatment.

MeSH Terms
Animals Burkitt Lymphoma/pathology Calcium-Binding Proteins/pharmacology Calreticulin Cattle Cell Division/drug effects Cell Line, Transformed Colonic Neoplasms/pathology Culture Media, Conditioned Endothelium/cytology,drug effects Endothelium, Vascular/cytology,drug effects Female Fibroblast Growth Factor 2/pharmacology Humans Mice Mice, Inbred BALB C Molecular Weight Neoplasms, Experimental/pathology Neovascularization, Pathologic/pathology Neovascularization, Physiologic/drug effects Peptide Fragments/pharmacology Recombinant Fusion Proteins/pharmacology Ribonucleoproteins/pharmacology Tumor Cells, Cultured Umbilical Veins/cytology,embryology
Chemicals
Calcium-Binding Proteins Calreticulin Culture Media, Conditioned Peptide Fragments Recombinant Fusion Proteins Ribonucleoproteins Fibroblast Growth Factor 2
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Pike S E
Center for Biologics Evaluation and Research, Rockville, Maryland 20852, USA.
Yao L
Jones K D
Cherney B
Appella E
Sakaguchi K
Nakhasi H
Teruya-Feldstein J
Wirth P
Gupta G
Tosato G
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.188.12.2349
Published
1998-12-21
Pages
2349-56
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212424
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.188.12.2349 PMC Full Text View journal details
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